OVERVIEW: What every practitioner needs to know

Are you sure your patient has an atrial septal defect? What are the typical findings for this disease?

For the purposes of this chapter, the information is most applicable to ostium secundum ASD (atrial septal defect). Important differences that are related to the location of the ASD will be described as appropriate.

It is unusual for children younger than 10 years of age to have symptoms related to an ostium secundum ASD. With each decade, though, patients with unrecognized or unrepaired ASD tend to have a higher prevalence of symptoms. 90% of patients older than 40 years of age have symptoms ascribed to the presence of an ASD.

The most common sign leading to the diagnosis of an atrial septal defect (ASD) is a heart murmur. Typically, in childhood there are no real symptoms of an ASD. The pathognomic sign of an ASD is a fixed split-second heart sound. A patient with an ASD may have a fixed split-second heart sound and have no heart murmur. The presence or absence of a systolic murmur is not reliably predictive of the size of the ASD.

The next most common clues leading to a diagnosis of an ASD are an abnormal electrocardiogram (ECG), typically showing right ventricular hypertrophy, or an abnormal chest roentgenogram showing cardiomegaly, usually with increased vascular markings but without pulmonary edema.

The diagnosis of ASD can be cryptic. ASD is the most common congenital heart defect, other than bicuspid aortic valve, to be discovered in adulthood.

Additional diagnostic information

In older children and adults, the finding of an ASD may be made after an ECG or a chest roentgenogram is obtained for reasons unrelated to clinical suspicion of congenital heart disease (e.g., a screening ECG before instituting drug therapy or a preoperative chest roentgenogram). Adults with an ASD may experience right ventricular failure. This is uncommon in the first decade of life. Atrial arrhythmias may occur in patients with a long-standing atrial level left-to-right shunt. Typically, the atrial arrhythmias encountered are related to long-standing right atrial enlargement. Atrial tachycardia, atrial flutter, and atrial fibrillation are the most common new arrhythmias in adults with unrepaired ASD.

The most common ASD is an ostium secundum ASD. Ostium secundum ASD occurs in 75%-85% of patients with an ASD. The next most common type of ASD is an ostium primum ASD. In some classification systems, an ostium primum ASD is included with atrioventricular (AV) septal defects (AV canal defects or endocardial cushion defects) rather than with ASDs.

A rational argument can be made to include ostium primum ASDs with AV septal defects because of the associated abnormalities of the AV valves, which are similar in ostium primum ASDs, transitional AV septal defects, and complete AV septal defects. If included among ASDs, approximately 10%-15% of ASDs are of the ostium primum type. Children with an ostium primum ASD typically present earlier than children with an ostium secundum ASD. The size of the defect in the atrial septum tends to be larger and the degree of left-to-right shunting and pulmonary overcirculation tends to be higher. Additionally, because of the presence of a cleft mitral valve, there may be a murmur of mitral insufficiency.

Sinus venosus ASD, which is typically associated with partial anomalous pulmonary venous connection, makes up approximately 5% of ASDs. Finally, there is a rare defect called coronary sinus ASD, which is a failure of development of the separation of the coronary sinus from the left atrium, which allows left atrial blood to enter the right atrium through the orifice of the coronary sinus. Although the physiologic characteristics are those of an atrial level left-to-right shunt, a more accurate description is unroofed coronary sinus.

Most children with an ASD are within the normal range for weight and height. The weight distribution of children with an ASD is not identical to the weight distribution of children without any disease.

Children with an ostium secundum ASD have a higher likelihood of being underweight. This does not always change with surgery or catheter closure.

What other disease/condition shares some of these symptoms?

In childhood, heart murmurs typically are normal findings. In fact, the murmur that is associated with an ASD may sound like a normal heart murmur. The factors that point toward the diagnosis of an ASD are other findings on examination such as a right ventricular heave on palpation, abnormal splitting of the second heart sound, or a diastolic filling sound.

Pulmonary valve stenosis also produces a murmur that is heard best in the same location as the murmur of an ASD (the left upper sternal border). Typically, pulmonary valve stenosis has an associated systolic ejection click, the murmur of pulmonary valve stenosis tends to be more harsh than the systolic murmur associated with an ASD, and diastole is quiet.

What caused this disease to develop at this time?

The primitive heart develops to form two atria through the formation of the two different septa, the septum secundum and the septum primum. Normally, during fetal life there is a connection between the two atria, even after the heart is fully developed. This is called the foramen ovale, which allows the blood returning from the placenta to cross the atrial septum from the right atrium to the left atrium so that oxygenated blood can reach the ascending aorta and subsequently reach the developing head and brain. If the septum secundum or the septum primum fail to develop normally, an ASD occurs.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

There are no laboratory studies that are important in the diagnosis of an ASD.

Would imaging studies be helpful? If so, which ones?

If an ASD is suspected on physical examination, the most useful confirmatory test is echocardiography.

The ECG typically is abnormal in the presence of a large ASD. Most patients have varying degrees of right ventricular hypertrophy on electrocardiography. Other findings on electrocardiography predict the likely location of the defect in the atrial septum. Patients with an ostium primum ASD often have left axis deviation of the frontal plane QRS axis. Patients with a sinus venosus ASD often have an abnormal P wave axis.

Chest roentgenograms may be abnormal, with right ventricular enlargement, right atrial enlargement, and enlargement of the central pulmonary arteries.

Confirming the diagnosis

The most common sign leading to a diagnosis of ASD is a heart murmur. Typically, this murmur is due to increased blood flow in the right ventricular outflow tract and main pulmonary artery. The murmur may be quiet or loud, but a thrill is absent. If a pulmonary flow murmur is present, the examiner should listen closely to the second heart sound.

Normally, the second heart should exhibits "physiologic splitting," which is related to variations in pulmonary vascular impedance changes between inspiration and expiration. Normally, during inspiration the total amount of blood that can be in the pulmonary vascular bed increases (increased capacitance), so the impedance drops. With exhalation, the capacitance drops and the impedance increases. When impedance drops, blood flows into the pulmonary vascular bed for a longer period so that P2 occurs later in the cardiac cycle.

In the presence of a signicant ASD, pulmonary capacitance is high throughout the respiratory cycle because increased pulmonary blood flow blunts the changes in capacitance related to changes in total lung volume. This means that impedance is always low. Therefore, P2 is always delayed, resulting in the physical examination finding of a fixed split-second heart sound. If there is a fixed split-second heart sound (with or without the additional finding of a pulmonary flow murmur), an echocardiogram should be obtained.

If you are able to confirm that the patient has an atrial septal defect, what treatment should be initiated?

In infancy, an isolated ASD typically does not need medical therapy. The right ventricle and the pulmonary circulation adapt to increased pulmonary blood flow without creating a need for urgent therapy. In patients in whom the ASD is large enough to warrant closure, closure is performed electively between age 2 and age 5 years.

Larger ASDs require closure. There are two options for closure. Surgical closure of an ASD was first introduced in the 1950s. Experienced congenital heart surgeons in dedicated congenital heart surgery programs have extremely good results with surgical closure, with low levels of complications and almost no mortality. A more recent development that has been available since the 1980s for isolated ostium secundum ASD is catheter-based closure. For defects that are centrally located in the atrial septum and are not overly large, this therapy is also safe and highly effective.

In the presence of an ostium secundum ASD, a general indication for closure (surgical or catheter) is the presence of right ventricular enlargement persisting beyond the age of 2 years. Generally, the presence or absence of right ventricular enlargement is determined by echocardiography.

Most ASDs that close spontaneously do so in the first year of life. An ASD that causes right ventricular enlargement generally is associated with a Qp:Qs ratio of greater that 1.5 or 1.8. (The Qp:Qs ratio is one way to assess the hemodynamic significance of a left-to-right shunt. Typically, this information is collected at cardiac catheterization, if necessary.) If the Qp:Qs ratio is low (<1.5) there is very limited data to support closure by surgery or catheterization.

What are the adverse effects associated with each treatment option?

Surgical closure of ASDs requires open heart surgery performed with the support of cardiopulmonary bypass. Potentially, there are many problems that could result from open heart surgery and cardiopulmonary bypass, which include the following:

Infection

Air embolus

Stroke

Damage to the heart or blood vessels surrounding the heart

Inadequate myocardial protection during cardioplegia

Bleeding

Incomplete repair

However, it is highly unlikely that surgery by an experienced congenital heart surgeon will result in any of these problems. ASD repair by a cardiac surgeon who is not an experienced congenital heart surgeon does appear to have increased risk and is not recommended.

Postoperatively, some patients will have evidence of inflammation that causes pericardial effusion (post–pericardiotomy syndrome).

Catheter-based closure is also generally safe and effective. There is an ongoing controversy about the appropriate selection of patients with an ostium secundum ASD for catheter-based closure versus surgical repair. Potential problems with cardiac catheterization and ASD closure device implantation include:

Infection

Stroke

Perforation of the wall of the heart

Damage to the mitral valve or the tricuspid valve

Arrhythmia

Incomplete repair

Bleeding

Damage to one of the blood vessels used to pass the catheter to the heart.

Again, physicians with extensive experience in ASD occlusion device placement are very unlikely to have any problems with closure and the long-term outcomes are typically outstanding.

What are the possible outcomes of an atrial septal defect?

A small ASD in a newborn is considered benign in almost every case. The importance of a small ASD in an older child is not certain but does not appear to be associated with intermediate-term consequences in the great majority of cases. An ASD that is detected in childhood and closed with either surgery or by catheter techniques should have no long-term impact on future health.

If there is right ventricular failure or atrial arrhythmia before repair (unusual in the first decade of life), it is possible for those abnormalities to persist after repair. However, even if these abnormalities persist after ASD closure, the clinical course appears to be enhanced compared with what would be expected without closure.

A prospective study demonstrated an ostium secundum ASD by echocardiography in 24/102 infants thought to have no heart disease. The first echocardiogram was performed at 2 to 7 days of age. Serial echocardiograms were performed throughout the first year of life. ASD diameter initially ranged from 3-8 mm. Eleven of 24 patients had spontaneous closure within 1 week. Twenty-two of 24 patients had spontaneous closure by 1 year of age. The two patients with persistent ASD had initial diameters of 5 mm and 6 mm. Only one patient (initial diameter of 6 mm) had evidence of significant left-to-right shunting.

What causes this disease and how frequent is it?

ASD is the second most common congenital heart defect diagnosed in childhood, ventricular septal defect being the most common. Approximately 10% of patients with congenital heart disease have an isolated ASD. Overall, ASD is much more common than this, but if the patient has an ASD and some more severe form of congenital heart disease (e.g., ventricular septal defect, pulmonary valve stenosis, transposition of the great arteries), the subject is classified under the more serious disease category and the ASD is ignored for the purposes of disease prevalence.

Holt-Oram syndrome, first described in 1960, is characterized by varying degrees of radial aplasia and abnormal cardiac septation, most classically an ostium secundum ASD. Subsequently, it was found that at least 75% of patients with Holt-Oram syndrome have abnormalites in TBX5, which is a transcription factor located on chromosome 12.

Mutations in NKX2.5, a gene coding for cardiac transcription located on chromosome 5, cause a familial form of ostium secundum ASD. 1% to 4% of ASDs are associated with mutations in NKX2.5 and 8%-19% of familial ASDs are associated with these mutations.

Most ASDs occur spontaneously and have no evidence of a genetic cause.

About half of the children born with Down syndrome have a congenital heart defect. The most common ASD present in children with Down syndrome is an ostium primum ASD.

How do these pathogens/genes/exposures cause the disease?

There is a female predominance in ASD, with twice as many girls having an ASD as boys.

The genes that are associated with ASD, listed above, code for transcription factors.

What complications might you expect from the disease or treatment of the disease?

There is an association of pulmonary vascular disease with ASD in adults. This association is rare before the age of 20 years. Most investigators believe that the presence of an ASD in a child with pulmonary hypertension is coincidental, rather than causing the pulmonary hypertension. In earlier natural history studies, 5% to 10% of adults with an ostium secundum ASD had significant elevation of pulmonary vascular resistance. This seems to be more common in people who live at high altitudes.

The exact role of the left-to-right shunt in causing pulmonary vascular disease is less certain in ASD than it is in other congenital heart defects, such as large ventricular septal defect, complete AV septal defect, or large patent ductus arteriosus, which result in elevations in pulmonary artery pressure caused by a connection between the systemic and pulmonary circulations after the level of the tricuspid valve.

The finding of pulmonary hypertension in a patient with an ASD, particularly in a child, should be followed by a careful investigation for other conditions that might signal the development of pulmonary vascular disease, such as chronic lung disease with hypoxemia, sleep apnea, or chronic thromboembolic disease. Children with Down syndrome also have an increased risk for pulmonary vascular disease, with or without congenital heart disease. The presence of congenital heart disease in Down syndrome increases the risk for pulmonary vascular disease beyond the baseline increased risk in Down syndrome.

How can atrial septal defect be prevented?

There is no known preventive strategy for atrial septal defect.

What is the evidence?

(This is one of many studies describing the incidence of congenital heart disease. This particular study has the advantage of a relatively consistent approach to diagnosis and of being a clinical level data set rather than drawing from an administrative data set.)

(The data is this study came from serial ECGs performed on a group of neonates not thought to have congenital heart disease who were followed for the first year of life. It demonstrates the high likelihood of spontaneous closure of an isolated ostium secundum ASD <8 mm in diameter discovered in the neonatal period.)

(Even after the first birthday, many children with small ASDs have spontaneous closure, and during intermediate follow-up not all children with a persistently patent ostium secundum ASD require surgical or catheter closure.)

(This article reports the long-term results of 123 patients who underwent repair of ostium secundum ASD at Mayo Clinic between 1956 and 1960. The long-term results were good even in those patients who underwent repair in the earliest days of open heart surgery. For patients who underwent repair before age 25 years, the actuarial survival of more than 27 years was no different than that of controls.)

Ongoing controversies regarding etiology, diagnosis, treatment

There are two dominant controversies regarding ostium secundum ASDs.

Is the preferred therapy for patients requiring closure of an ostium secundum ASD open heart surgery or placement of a percutaneious ASD closure device? This controversy is relevant only to ostium secundum ASDs, as the other types of ASDs are not appropriate for catheter-based closure. There is no study that truly answers the question of either a safety advantage or an efficacy advantage for one therapy over the other. Generally, both therapies are safe and effective. Extremely large ASDs or ASDs that are not centrally located in the atrial septum are not best served with catheter-based closure strategies.

What are the indications for closure in a patient with an ostium secundum ASD when the defect is not large (no right ventricular enlargement or a Qp:Qs ratio <1.5)? There is no evidence that closing a small ASD, or closing an ASD with a small left-to-right shunt has any favorable effect on intermediate-term outcomes.

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